title: Design, synthesis, and biological evaluation of acetophenone derivatives as dual binding acetylcholinesterase inhibitors.
abstract: As part of a project aimed at developing new agents for potential application in Alzheimer's disease, a new series of acetophenone derivatives which possess alkylamine side chains were designed, synthesized and assayed as acetylcholinesterase (AChE) inhibitors that could simultaneously bind to the peripheral and catalytic sites of the enzyme. The compounds were synthesized, and the inhibitory activities toward AChE and butyrylcholinesterase (BuChE) in vitro were determined using a modified Ellman method. Of the compounds tested, 6 derivatives were found to inhibit AChE in the micromolar range. The best compound, 2e, had an 1C50 of 0.13 microM. A detailed molecular modeling study was performed to explore the interaction of 2e with AChE.
authors.affiliation: College of Chemistry and Environmental Science, Anyang Institute of Technology, Anyang 455000, China. yanhong0809@163.com
authors.forename: Yanhong
authors.initials: Y
authors.lastname: Shen
authors.forename: Baoli
authors.initials: B
authors.lastname: Li
authors.forename: Hu
authors.initials: H
authors.lastname: Xu
authors.forename: Guoqiang
authors.initials: G
authors.lastname: Zhang
mesh_terms: D000098:Acetophenones / Q000138:chemical synthesis* / Q000494:pharmacology*; D000110:Acetylcholinesterase / Q000378:metabolism; D000818:Animals; D001921:Brain / Q000187:drug effects / Q000201:enzymology; D002091:Butyrylcholinesterase / Q000378:metabolism; D002800:Cholinesterase Inhibitors / Q000138:chemical synthesis* / Q000494:pharmacology*; D015195:Drug Design; D007202:Indicators and Reagents; D008958:Models, Molecular; D051381:Rats; D013329:Structure-Activity Relationship
chemical_list: D000098:Acetophenones; D002800:Cholinesterase Inhibitors; D007202:Indicators and Reagents; D000110:Acetylcholinesterase; D002091:Butyrylcholinesterase